The Relationships among MRI‐Defined Spinal Cord Involvement, Brain Involvement, and Disability in Multiple Sclerosis

Abstract

Objective To determine the inter-relationships between MRI-defined lesion and atrophy measures of spinal cord involvement and brain involvement and their relationships to disability in a small cohort of patients with multiple sclerosis (MS). Background Although it is known that cervical spinal cord atrophy correlates with disability in MS, it is unknown whether it is the most important determinant when compared to other regions of the CNS. Furthermore, it is not clear to what extent brain and cord lesions and atrophy are related. Design/methods 3T MRI of the whole brain and whole spinal cord was obtained in 21 patients with MS, including 18 with relapsing-remitting, one with secondary progressive, one with primary progressive, and one with a clinically isolated syndrome. Brain global gray and white matter volumes were segmented with SPM8. Spinal cord contour volume was segmented in whole by a semi-automated method with bins assigned to either the cervical or thoracic regions. All CNS volumes were normalized by the intracranial volume. Brain and cord T2 hyperintense lesions were segmented using a semi-automated edge finding tool. Results Among all MRI measures, only upper cervical spinal cord volume significantly correlated with Expanded Disability Status Scale score (r=−0.515, p=0.020). The brain-cord relationships between whole or regional spinal cord volume or lesions and gray matter, white matter, or whole brain volume or whole brain lesions were generally weak and all non-significant. Conclusions/relevance In this preliminary study of mildly disabled, treated MS patients, cervical spinal cord atrophy most strongly correlates with physical disability in MS when accounting for a wide range of other CNS measures of lesions and atrophy, including thoracic or whole spinal cord volume, and cerebral gray, white or whole brain volume. The weak relationship between spinal cord and brain lesions and atrophy may suggest that they progress rather independently in patients with MS.

Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis

“…23,24 Considering region-specific pathologic differences, prior studies have found limited correlations between measures of SC and brain atrophy (SC-CSA and BPF), suggesting that pathogenic mechanisms in MS evolve independently to an extent in the brain and SC, particularly in progressive phases of disease, supporting the idea that MS disease mechanisms may differentially affect specific regions of the CNS. 14,25,26 Our observations of moderate correlations between SC and retinal measures, but absent correlations between measures of SC and brain atrophy support the notion that MS disease pathology is nonuniform in distinct CNS compartments, 27,28 and suggest there are clinically relevant pathologic processes occurring in the SC and retina that are distinct from those in the brain. Moreover, our observations of stronger SC and retinal correlations in progressive patients support the view that immunopathologic and tissue injury mechanisms of MS differ by disease subtype, and may be indicative of more uniform pathologic changes occurring in PPMS and SPMS, although these progressive MS subtypes may not be equivalent pathologically.…”

Spinal Cord as an Adjunct to Brain Magnetic Resonance Imaging in Defining “No Evidence of Disease Activity” in Multiple Sclerosis

“…The spinal cord is a common site of pathology in MS, occurring early in the disease course 12,25 and playing a role in the development of disability 11,[14][15][16][17]19,[21][22][23]28 ; such involvement includes overt multifocal inflammatory demyelinating lesions and the potential for tissue destruction (axonal loss/atrophy). 29 This study evaluated the role of brain and spinal cord 3T MRI in defining NEDA at 1 year.…”

“…10 A growing body of evidence has determined that spinal cord MRI involvement shows a particularly close association with MSrelated disability. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] In addition, spinal cord involvement manifests early in the disease course; such lesions in presymptomatic at-risk individuals predict conversion to overt MS. 25 Adding more relevance to the need to consider spinal cord involvement in MS is the observation that such involvement may progress independently from the brain.…”

Atrophy

“…Only moderate correlations have been found between cervical cord atrophy and conventional and advanced MRI measures of brain damage, 45,46,51 suggesting that degenerative and inflammatory processes typical of MS affect the cord and the brain with dynamics that are partially independent.…”